Image-guided treatment planning for pleural Photodynamic Therapy Abstract The overall objective of this grant is to develop an integrated system for real-time PDT dosimetry and light source monitoring during intracavitary photodynamic therapy. We propose to develop an infra- red camera-based system for real-time tracking of the motion of the light source used for treatment. The same tracking system will be used to digitize the surface contour of the cavity being treated for light fluence rate calculation. An optical fiber-based spectroscopic probe, coupled with the IR camera tracking device, will be used to determine absorption spectra at multiple points on the pleural cavity surface before and after PDT. Analysis of the absorption spectrum will determine the tissue oxygenation and the sensitizer concentration at these points. The same probe will be capable of performing fluorescence spectroscopy to verify drug concentration in-vivo before and after PDT. The absorption spectrum will also be used to determine the tissue optical properties in-vivo and use these points as input for light fluence rate calculation. To improve the spatial resolution of the heterogeneous tissue optical properties, we plan to develop a spectral reflectance imaging system to determine the surface distribution of optical properties in tissue before and after PDT. The temporal variations of light fluence rate, absorption spectrum, and fluorescence emission will be measured in- vivo at 7 selected points and compared with calculations using a light fluence calculation algorithm which takes into account the geometry and optical properties of the cavity. PDT dose will be calculated as a product of drug concentration and light fluence rate. We hypothesize that using PDT dose as a PDT dosimetry quantity to optimize light source movement will result in improvement of the spatial uniformity of PDT treatment and thus its efficacy. Further improvement of the PDT dose by a new dosimetric quantity, reacted singlet oxygen concentration that takes into account of light fluence rate effect, will be examined in a preclinical model. PUBLIC HEALTH RELEVANCE: Relevance Statement: Pleural cancer is a serious public health problem for which there is no curative treatment available. Photodynamic therapy in combination with surgery offers a potential locally curative treatment, which has been demonstrated to substantially prolong patient's lives. The result of this project will substantially improve the light delivery homogeneity and quantification of PDT dose for pleural PDT, potentially resulting improved effectiveness of PDT as a curative therapy.